Lecture 19 Microbial Cardiovascular, Lymph, Systemic Diseases PDF

Microbial Cardiovascular, Lymphatic and systemic Diseases  Septicemia and Septic Shock Blood is normally sterile: – a few microbes are OK, because of the presence of defensive phagocytic cells and lack of freely available iron for growth of microbes (iron is in RB...

Microbial Cardiovascular, Lymphatic and systemic Diseases  Septicemia and Septic Shock Blood is normally sterile: – a few microbes are OK, because of the presence of defensive phagocytic cells and lack of freely available iron for growth of microbes (iron is in RBC) Septicemia (sepsis): toxic condition from uncontrolled bacterial proliferation in blood due to failure of defenses and cytokines are released Tachypnea – symptoms: chills, fever, accelerated breathing and heart rate euypnea = normal breathing bradypnea = slow breathing Severe sepsis: when sepsis results in drop in blood pressure and dysfunction of at least one organ – low blood pressure can still be controlled by adding fluids Septic Shock: final stage of sepsis – blood pressure can no longer be controlled by adding fluids – multi-organ failure often occurs, very high mortality rate  Lymphangitis Lymphangitis: Infection Lymphangitis is a sign and inflammation of the of septicemia lymphatic vessels As microbes travel through lymphatic vessels, from a site of infection, localized inflammation occurs. Septicemia refers to any microbial infection of the blood. Bacteremia is bacterial septicemia  Septicemia and Toxemia Caused by various bacteria: – pathogens are often opportunistic or nosocomial infections – septicemia acquired by direct inoculation of bacteria into blood Ex. medical procedures, drug users – Immunocompetent individuals rarely have septicemia Bacterial infections in these people are self-limited Signs and symptoms: – Fever, chills, nausea, vomiting, diarrhea, malaise – Petechiae can develop – Osteomyelitis can occur when bacteria invade the bones  Gram-negative Gram-positive Sepsis Sepsis all gram negatives can cause sepsis Gram-negative bacteria: most Staphylococci and common cause of sepsis Streptococci can both cause – more likely to produce severe septicemia due to release of toxic shock syndrome endotoxin (LPS) as the bacteria die G+ bacteria can enter – LPS activates various defensive bloodstream from invasive reactions by the body procedures – endotoxic shock due to release of – kidney dialysis, iv devices, LPS from G- cell wall etc. 250,000 fatal cases of septic known shock per year in USA – G+ cell wall components, No effective treatment exists bacterial DNA – early symptoms are non-specific Enterococcus sp. therefore may not be diagnosed in – Problem: many penicillin time AND vancomycin resistant – administration of antibiotics at later stages may aggravate symptoms Streptococcus agalactiae Potential effects of endotoxin hyperactive clotting  Endocarditis Endocardium: epithelial layer lining heart muscle & covering valves Subacute bacterial endocarditis: Acute bacterial endocarditis: slow development rapid progression viridans α-hemolytic Streptococci, S. aureus biofilm formation Staphylococci, Enterococci bacteria migrate from focus of infection fever, weakness, heart murmur normal and abnormal valves are usually starts w/ focus of infection affected elsewhere in body untreated: fatal within days – tooth extraction, tonsillectomies prophylactic penicillin sometimes abnormal heart valves ↑ risk used congential heart problems, you are given prophylaxis before a surgery bacteria lodge in blood clots – tonsillectomies, tooth extractions – protected from immune system fatal in a couple months if untreated  Rheumatic Fever s. pyogenes Follows Group A Streptococcal pharyngitis – Abs cross-react between strep Ags & host heart valves (autoimmune) – age 4-18 most susceptible Sore throat  short period of arthritis, fever – subcutaneous nodules at joints may be present at this stage Inflammation of heart in ~50% of cases – valve damage Glomerulonephritis: due to immune complex formation from anti-streptococcal Abs Reinfection w/ Streptococci can renew immune attack – monthly prophylactic penicillin injections Heart damage may be fatal  Gangrene systemic Commonly caused by Clostridium perfringens obligate anerobes – Gram +, endospore-forming, anaerobic bacillus – 12 toxins – generally introduced by trauma, injection sites, surgery Gangrene: death of soft tissue in part of the body. – happens with ischemia (interruption in blood flow and loss of blood supply to tissue) necrosis of affected tissue – necrotic tissue provides nutrients for bacterial growth – perfect conditions for growth of C. perfringens anaerobic environment , lots of nutrients released from dead/dying cells  Gangrene most people with gas gangrene get it from serious accidents C. perfringens ferments carbohydrates to CO2 and H2 leading to tissue swelling and gas bubbles = Gas gangrene Virulence factors: gas gangrene in uterine wall  – toxins, collagenase, complication of improperly proteinase performed abortions Systemic illness: septicemia, – C. perfringes normal flora in toxemia genital tract of ~5% of women Symptoms – leads to life-threatening infection of bloodstream – extreme pain treatment: – weeping bullae; – debridement, amputation brownish foul- – hyperbaric chamber for smelling discharge abdominal cavity infections – hypotension – IV antibiotics – massive hemolysis  jaundice, black urine  Plague Black Death, Bubonic plague – hemorrhages cause dark areas Yersinia pestis – G- coccobacillus reservoirs: rodents, prairie dogs, squirrels, cats – transmitted by fleas – if host dies flea seeks new host – can jump 3.5” – can also spread by direct contact with animals bubonic, pneumonic, septicemic, meningeal flea bite  bacteremia  proliferate in lymph & blood – survive and proliferate inside of phagocytic cells (T3SS, injects Yops in macrophages) – large # of virulent organisms produced – organisms emerge & overwhelming infection results  Bubonic Plague Signs & symptoms: – fevers, chills, headache swollen lymphs – 24 hours: massive buboes usually near inoculation site – progress to multisystem disease sepsis, hypotension, DIC, encephalitis, diarrhea, pneumonia  Plague septicemic plague: septic shock due to bacterial proliferation in blood – untreated: mortality rate of 50-75% pneumonic plague: bacteria can be carried via blood to lungs – mortality ~100% even today unless recognized w/in 12-15 hr – death usually within 3 days – easily spread by airborne droplets from humans or animals treatment: – i.v. gentamicin or streptomycin or doxycycline – prophylactic antibiotic protection following exposure (contacts of respiratory patients) recovery = immunity – vaccine available for high risk workers wound infections / surgical wound infections complications: secondary infection of buboes (S. aureus)  Lyme Disease Bacterial pathogen: Borrelia burgdorferi – Spirochete tick-borne disease first diagnosed as rheumatoid arthritis – young people – seasonal occurrence (summer) – not contagious among family members – unusual rash prior to onset of symptoms – symptom progression alleviated by penicillin  Lyme Disease Symptoms: 1st phase: – “bull’s-eye” rash at bite site erythemia chronicum migrans – flu-like symptoms as rash disappears 2nd phase: – cardiac: (myocarditis)irregular heartbeat  pacemaker – neurological: facial paralysis, meningitis, encephalitis – arthritis may develop months or years later due to immune response against bacteria Treatment: progression to 2nd phase can be prevented by antibiotics in 1st phase various combinations of antibiotics depending on stage and symptoms  Epstein-Barr Virus (EBV) Burkitt’s Lymphoma – HHV-4 – EBV isolated from tumors of Burkitt’s lymphoma first link between virus & human cancer EBV mechanism of tumor formation not well understood – malarial infections may facilitate development of Burkitt’s lymphoma by impairment of EBV-directed immune response – disease is rare in absence of endemic malaria  Epstein-Barr Virus (EBV) kissing disease Infectious mononucleosis (“mono”) – often acquired during childhood – exposure during adolescence tends to be more symptomatic – fewer people in developed countries display immunity sore throat, fever, swollen neck lymph nodes, general weakness lymphoadenopathy incubation 4-7 weeks EBV multiplies within B cells *ATYPICAL LYMPHOCYTES = reactive T cells usually self-limiting, infection = immunity seldom fatal death may be caused by splenic rupture during vigorous activity  Cytomegalovirus (CMV) Human Herpesvirus 5 primary CMV infection during CMV remains latent in leukocytes pregnancy – infected cells have distinct ‘inclusion serious damage to fetus can result bodies’, visible by microscopy severe mental retardation, – the infected cells swell (cyto=cell, hearing loss megaly=enlargement) enlarged liver and spleen ~80% of population in North America (hepatosplenomegaly) carries CMV transmission – mild or asymptomatic disease in healthy adults body fluids: saliva, semen, breast – infection is normally contained by host milk immune response kissing, sexual contact, transfused CMV is a common opportunistic blood, transplanted tissue pathogen Treatment: – reactivates when host becomes antivirals such as gancyclovir in immunocompromised immunocompromised transplantation recipients: pneumonia treatment may be lifelong Majority of AIDS patients exhibit CMV retinitis which can result in vision loss Vaccine: under development but none available yet  Toxoplasmosis can cross placenta caused by Toxoplasma gondii (protozoan) cat = definitive host – large number of urban cats infected (no symptoms in cat) – microbe lives in GI tract of cat  shed in cat feces  contaminate food/water sources  ingested by other animals ~40% of population has Abs to T. gondii – in healthy people – mild or no symptoms T. gondii forms cysts in tissue – infection can be reactivated from cysts in immunocompromised people – vision damage, neurological damage (cyst location) if initial infection in acquired during pregnancy: – congenital infection: stillbirth, brain damage, vision problems – In Europe if acquired during pregnancy, abortion is encouraged  Schistosomiasis debilitating disease caused by fluke: Schistosoma sp. specific species of snail is required for part of life cycle spread through contaminated water – eggs from human feces or urine – problem in areas of poor sanitation schisto-some = “split body” – female lives permanently in groove in male worms may live 20 years – constantly produce eggs some eggs lodge in tissues some excreted ending up in H2O supply different species cause damage to different organs depends on egg migration: liver, lungs, urinary bladder, brain  Schistosomiasis adult worms avoid immune system by coating themselves with a layer that mimics host tissues drugs, sanitation, elimination of host snail are means of control of this infection clinical manifestations – papular skin rash at penetration site (lasts 24-48 hours) – fever, chills, headaches, cough begins 4-8 weeks after infection; lasts 2-4 weeks immune reaction to eggs – chronic phase (lasts many years) abdominal pain, diarrhea liver failure (eggs pass through liver) pulmonary hypertension (eggs in lungs) urinary obstruction, renal failure CNS symptoms (eggs in brain)  Zoonosis Brucellosis up and down fever (high temp and low temp) Brucellosis (undulant fever).  Small, Gram-ve rods;  no capsule  flagellated  Aerobic  Facultative intracellular pathogen hides inside of cells  Survive outside the host in extreme temperature, pH and humidity  Potentially bio-warfare agent  Brucellosis major human pathogens are:  B. melitensis (reservoir = goats & sheep);  B. abortus (cattle);  B. suis (pigs or swine)  B. Canis (dogs) goat milk and cheese  Enter body by ingestion of contaminated milk products, or by direct through skin in occupational setting e.g. in abattoir.  Pathogenesis, epidemiology, The bacterium enters the body through breaks in mucous membranes of the digestive and respiratory tracts It travels inside phagocytic cells to organs of the body including lymph nodes, spleen, bone marrow, liver, and heart. Diseases: Arthritis Splenomegaly Enlarged testes, Endocarditis Meningitis and encephalitis (rare cases)  Treatment, prevention Treatment Use doxycycline and rifampin or streptomycin for weeks Prevention Attenuated vaccine for animals Pasteurization of milk slaughtering of infected animals No human vaccine available  Tularemia Bacteria: Francisella tularensis  F. tularensis is small, pleomorphic, Gram –ve rod.  Strict aerobe  Single serologic type.  Enzootic in every US state.  Most important animal reservoirs are rabbits, deer & rodents.  Vectored between animals by ticks, mites & lice, especially Dermacentor, a tick that feeds on wild rabbits.  Pathogenesis  Most frequent form in US is tick-borne tularaemia from rabbit.  Entry usually through skin; ulcer formed at site of entry in most cases.  Bacteria then localise in typo, should be rectoendothelial system resulting in formation of recticuloendothelial granulomas.  Abscesses & caseation tissue breakdown into cheese-like formation can occur.  Symptoms  Symptoms vary from rapid onset of influenza- like illness to prolonged onset of mild fever & adenopathy. enlargement of lymph nodes ulcers and enlargement of glands   75% of cases are ulceroglandular; i.e. site of entry ulcerates & local lymph nodes become swollen & painful.  Glandular, oculoglandular, typhoidal, gastrointestinal & pul monary tularaemia occur but are rarer.  Disease usually results in immunity for life.  Treatment and prevention  Streptomycin is the drug of choice.  No significant resistance reported.  Can be prevented by avoiding tick bites & handling of wild animals..  Experimental live, attenuated vaccine is given to individuals whose occupation puts them at risk – e.g., fur trappers.